Hyperbilirubinemia is probably the most frequent disease which is diagnosed and treated in the human newborn. Current treatment attempts to prevent neurologic damage. Treatment is based on the theory that free (unbound) bilirubin is the toxic fraction of the total bilirubin pool. Proof of this theory is lacking, and certain clinical and experimental findings are not consistent with the theory. Another hypothesis better explains the available data: bilirubin enters the brain bound to albumin when the blood-brain barrier opens. This hypothesis is amenable to experimental testing.